CD137 Identifies and Enriches for Tumor-Reactive T Cells

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In a study reported in Clinical Cancer Research, Ye and colleagues showed that CD137 can be used to identify tumor-reactive T cells and to enrich for tumor-infiltrating lymphocytes and tumor-associated lymphocytes for use in adoptive immunotherapy.

In the study, tumor-infiltrating lymphocytes from resected ovarian cancer or melanoma were measured for surface CD137 expression directly or after incubation with tumor cells and cytokines. CD137-positive tumor-infiltrating lymphocytes were sorted and evaluated for antitumor activity.

In ovarian cancer studies, fresh tumor-infiltrating lymphocytes and tumor-associated lymphocytes expressed higher levels of CD137 vs circulating T cells. There was an HLA-dependent increase in CD137 expression after incubation of enzyme-digested tumor or ascites in interleukin [IL]-7 and IL-15 but not IL-2. Autologous tumor reactivity in vitro and in vivo was observed with enriched CD137-positive tumor-infiltrating lymphocytes, but not with PD-1–positive or PD-1–negative CD137-negative cells.

In melanoma studies, CD137 expression was increased in MART-1-specific CD8-positive tumor-infiltrating lymphocytes after incubation with HLA-matched MART-expressing cancer cells, with antigen-specific effector function being restricted to CD137-positive cells. CD137-positive cells induced greater antitumor effects in vivo compared with CD137-negative cells.

The investigators concluded, “Our findings reveal a role for the [tumor necrosis factor receptor]-family member CD137 in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of [tumor-infiltrating lymphocytes], thus rationalizing its agonistic engagement in vivo and its use in tumor-infiltrating lymphocyte selection for adoptive immunotherapy trials.” ■

Ye Q, et al: Clin Cancer Res 20:44-55, 2014.